RESUMEN
BACKGROUND: Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases. METHODS: RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways. RESULTS: COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages. CONCLUSIONS: The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity.
Asunto(s)
COVID-19 , Estudio de Asociación del Genoma Completo , Lupus Eritematoso Sistémico , SARS-CoV-2 , Transducción de Señal , Humanos , COVID-19/genética , Lupus Eritematoso Sistémico/genética , SARS-CoV-2/fisiología , Femenino , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Factores de Transcripción STAT/genética , Masculino , Transcriptoma , Perfilación de la Expresión Génica , MultiómicaRESUMEN
OBJECTIVE: To investigate the blood cadmium concentrations and the related change in Chinese urban children derived from the China Nutrition and Health Survey 2002 and 2012(CNHS 2002 and CNHS 2012). METHODS: The Chinese urban children aged 6-11 years were selected according to gender, age and regional distribution using the multi-stage stratified cluster random sampling method, as well as the corresponding whole blood samples. The blood cadmium concentration was carefully determined by the quadrupole inductively coupled plasma mass spectrometry(ICP-MS) and the percentage of blood cadmium over 2 µg/L was subsequently estimated. In addition, the upper limit values of the 95%CI of the 95th percentiles of available blood cadmium data was assessed as the threshold of cadmium exposure. RESULTS: Totally, 2182 Chinese urban children were included, and of these, 1036 children were from the CNHS 2002 and 1146 children were from the CNHS 2012. From the CNHS 2002 to the CNHS 2012, the median blood cadmium concentration was increased from 0.28 µg/L to 0.95 µg/L, and the percentage of blood cadmium with over 2 µg/L was elevated from 1.45% to 10.47%. In addition, the new estimated threshold of blood cadmium was ascended from 1.24 µg/L up to 2.89 µg/L. CONCLUSION: The risk of cadmium exposure in Chinese urban children aged 6-11 years was increasingly aggravated from the CHNS 2002 to the CNHS 2012.
Asunto(s)
Cadmio , Exposición a Riesgos Ambientales , Niño , Humanos , Cadmio/sangre , China , Pueblos del Este de AsiaRESUMEN
OBJECTIVES: To evaluate the differences in efficacy and safety between Lupus Nephritis (LN) patients who received belimumab plus standard therapy and those who received only standard therapy in real world practice. METHODS: Patients diagnosed with LN at the First Affiliated Hospital of Wenzhou Medical University from November 2012 to July 2023 were identified, and eligible cases were divided into two groups according to whether they received additional treatment with belimumab during the course of the disease. RESULTS: A total of 1,169 LN patients were identified from our follow-up database. 112 patients receiving add-on treatment with belimumab (BLM group) and 112 control patients matched for relevant baseline characteristics were enrolled in this study. The median duration of treatment with belimumab was 13.82 [7.24, 20.29] months. Compared with the control group, the BLM group had more significant improvement in disease activity indicators such as serum albumin and complement levels, significantly lower B cell count, immunoglobulin, and earlier first attainment of renal remission, but there was no significant improvement in renal function and kidney-related events or death during the 2-year follow-up period. In the BLM group, the treatment effect of belimumab was more prominent in patients with lower levels of proteinuria. The safety profile of belimumab treatment was favorable, with a lower incidence of respiratory tract infection in the BLM group than in the control group during the follow-up period (p= 0.015). CONCLUSIONS: This real-world study revealed that add-on treatment with belimumab provided better disease remission, and the therapeutic effect was more significant in patients with lower proteinuria levels. In addition, it had a favorable safety profile and reduced the risk of respiratory tract infection.
RESUMEN
OBJECTIVE: To assess the plasma selenium(Se) level of child-bearing-aged women and discuss the influence factor for low-Se level. METHODS: Using the muti-stage stratified and population proportional cluster random sampling method, 1881 child-bearing-aged women aged 18 to 44 years were selected from China Adult Chronic Disease and Nutrition Surveillance(2015) Data. The basic information of the subjects was collected by unified electronic questionnaires and equipments were used for field survey, measurement and record. Plasma Se concentration was detected by inductively coupled plasma mass spectrometry. Plasma low-Se level were assessed using lower limit of plasma/serum Se established by the Mayo Clinic Laboratory and our laboratory, respectively. Influence factors of low-Se level were analyzed by the multivariate logistic regression model. RESULTS: The M(P25, P75) plasma Se concentration for Chinese child-bearing-aged women was 89.52(74.21, 105.03)µg/L. Nationality, location, urban-rural type and education level difference had influence on plasma Se level in this population(P<0.05). According to the lower limit of plasma/serum Se concentration established by the Mayo clinical laboratories(<70 µg/L) and our laboratories(<73.81 µg/L), the low-Se rate were 20.47% and 24.51%, respectively. There were significantly differences in low-Se rate among nationality, location, urban-rural type, education level and marital status(P<0.05). The multivariate logistic regression model showed that location and urban-rural type had significant effects on low-Se rate of child-bearing-aged women(P<0.05). CONCLUSION: The plasma low-Se rate of Chinese women of childbearing age is relatively high and higher prevalence low-Se was found in western and central regions and rural areas in China.
Asunto(s)
Selenio , Adulto , Femenino , Humanos , Pueblo Asiatico , China/epidemiología , Pueblos del Este de Asia , Selenio/sangre , Encuestas y Cuestionarios , Adolescente , Adulto JovenRESUMEN
OBJECTIVE: Lupus nephritis (LN) is a major end-organ complication of systemic lupus erythematosus (SLE), and the molecular mechanism of LN is not completely clear. Accumulating pieces of evidence indicate the potential vital role of tRNA-derived small RNAs (tsRNAs) in human diseases. Current study aimed to investigate the potential roles of tsRNAs in LN. METHODS: We herein employed high-throughput sequencing to screen the expression profiles of tsRNAs in renal tissues of the LN and control groups. To validate the sequencing data, we performed quantitative real-time PCR (qRT-PCR) analysis. Correlational analysis of verified tsRNAs expression and clinical indicators was conducted using linear regression. The potential target genes were also predicted. The biological functions of tsRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: Our findings revealed that the expression profiles of tsRNAs were significantly altered in the kidney tissues from LN patients compared with control. Overall, 160 tsRNAs were significantly dysregulated in the LN group, of which 79 were upregulated, whereas 81 were downregulated. Subsequent qRT-PCR results confirmed the different expression of candidate tsRNAs. Correlation analysis results found that expression of verified tsRNAs were correlated to clinical indicators. The target prediction results revealed that verified tsRNAs might act on 712 target genes. Further bioinformatics analysis uncovered tsRNAs might participate in the pathogenesis of LN through several associated pathways, including cell adhesion molecules, MAPK signaling pathway, PI3K-Akt signaling pathway and B cell receptor signaling pathway. CONCLUSION: This study provides a novel insight for studying the mechanism of LN.
Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Fosfatidilinositol 3-Quinasas/genética , Ontología de Genes , Humanos , Nefritis Lúpica/genética , Fosfatidilinositol 3-Quinasas/química , Fosfatidilinositol 3-Quinasas/metabolismo , ARN de Transferencia/genéticaRESUMEN
OBJECTIVE: To investigate the association of rs7041 polymorphism of GC gene that encodes the vitamin D-binding protein with serum vitamin D status in Chinese women of childbearing age. METHODS: A total of 1812 plasma samples of women childbearing aged 18-44 years old were selected by stratified random sampling technology from the established biological samples bank of Chinese Chronic Diseases and Nutrition Survey(CCDNS, 2015-2018). The serum 25(OH)D status was detected by enzyme-linked immunosorbent assay. The genotypes of rs7041 in the GC gene were analyzed by improved multiple ligase detection reaction method. RESULTS: A total of 1812 childbearing women aged 18-49 years were included in this study. The frequency of rs7041 genotypes in the study were distributed according to the Hardy-Weinberg equilibrium, indicating sufficient representativeness of our sample. The median serum 25(OH)D status was 16. 69(12. 04, 21. 69)ng/mL. The higher 25(OH)D levels was detected in the overall sample, southern women or women with normal vitamin D status with the CC genotype than the AA genotype(P<0. 05). Before and after correction, the risk of vitamin D insufficiency in the women carrying the CC genotype was decreased significantly compared with the women carrying the AA genotype(OR=0. 571, 95%CI 0. 373-0. 873). And the CC genotype of rs7041 was associated with a significant decrease in risk of 25(OH)D deficiency(in the subgroup of southern childbearing women, OR=0. 284, 95%CI 0. 144-0. 560 and in the subgroup of northern childbearing women, OR=0. 109, 95%CI 0. 015-0. 798). CONCLUSION: The GC rs7041 with A/C polymorphism are significantly correlated with 25(OH)D status in Chinese childbearing women, mutant CC genotype is a protective factor for vitamin D non-normal status risks.
Asunto(s)
Polimorfismo de Nucleótido Simple , Vitamina D , Adolescente , Adulto , Pueblo Asiatico/genética , China , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Proteína de Unión a Vitamina D/genética , Adulto JovenRESUMEN
OBJECTIVE: To estimate the distribution of serum zinc levels, zinc deficiency status and possible influencing factors in 18-60 year-old adults in China. METHODS: Based on the data of China Adult Chronic Disease and Nutrition Surveillance, 3903 blood samples were selected by stratified random sampling. The distribution of serum zinc in adults with different gender, age, regional type and regional distribution were analyzed by inductively coupled plasma mass spectrometry and body mass index(BMI), exercise, smoking, drinking, vitamin A level and other factors on serum zinc concentration and zinc deficiency rate. Multivariate logistic regression model was used to analyze the correlation between zinc deficiency and the influencing factors. RESULTS: In 2015, the median of serum zinc in Chinese adults aged 18-60 years was 103. 44(95%CI 64. 84-186. 12) µg/dL, and the overall zinc deficiency rate was 6. 04%. Serum zinc concentration had statistically significant difference(P<0. 05) in different genders, regional types, regional distribution, vitamin A status, smoking status, drinking status. In the comparison of zinc deficiency rates, ethnic minorities(10. 67 %) was higher than Han(5. 44%), rural area(7. 35%) was higher than urban area(4. 90%), vitamin A deficiency group(9. 12%) was higher than vitamin A normal group(5. 90%), non-exercise group(6. 29%) was higher than sports group(5. 09%). Among different regional distributions, the western region had the highest zinc deficiency rate(7. 33%), and among different BMI groups overweight group had the lowest rate(4. 81%). These differences were statistically significant(P<0. 05). In the analysis of multivariate logistic regression, the risk of zinc deficiency in the vitamin A deficiency group was 1. 89 higher than that of the normal group(OR=1. 89, 95%CI 1. 13-3. 18); and the overweight group had a lower risk of serum zinc deficiency than the normal group(OR=0. 71, 95%CI 0. 52-0. 96). CONCLUSION: The prevalence of serum zinc deficiency among adults aged 18-60 in China is relatively low. Vitamin A deficiency is a risk factor for zinc deficiency and overweight is a protective factor for zinc deficiency.
Asunto(s)
Deficiencia de Vitamina A , Zinc , Adolescente , Adulto , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Prevalencia , Vitamina A , Deficiencia de Vitamina A/epidemiología , Adulto JovenRESUMEN
Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the 'iodine overflow' hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 µg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 µg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for µg/d data) and retention (r 0·304 for µg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted ('overflow') through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 µg/d) might be adequate in males, the corresponding level of 61·6 µg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 µg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the 'iodine overflow' hypothesis.
Asunto(s)
Ingestión de Alimentos/fisiología , Yodo/administración & dosificación , Yodo/análisis , Necesidades Nutricionales/fisiología , Adolescente , Adulto , Pueblo Asiatico , China , Dieta/métodos , Relación Dosis-Respuesta a Droga , Ayuno/sangre , Ayuno/orina , Heces/química , Femenino , Voluntarios Sanos , Humanos , Masculino , Factores Sexuales , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/análisis , Pruebas de Función de la Tiroides , Adulto JovenRESUMEN
OBJECTIVE: Comparison of liquid chromatography-tandem mass spectrometry(LC-MS/MS) and enzyme-linked immunosorbent assay(ELISA) for the detection of 25(OH)D concentration in human serum and the diagnosis of vitamin D deficiency. METHODS: In the serum pool of "National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention", 500 serum samples of women aged 18 to 45 years old were randomly selected, and 25(OH)D levels were measured by ELISA and LC-MS/MS for the same serum sample, respectively. The LC-MS/MS column was Waters XBridge BEH C_(18)(2. 1 mm×50 mm, 2. 5 µm). The correlation between the two method was tested by correlation analysis, regression analysis and consistency test. The Endocrine Society and Institute of Medicine recommendations were used to determine the deficiency of vitamin D, and the McNemar test, Kappa coefficient and diagnostic test were used to diagnose the consistency of vitamin D deficiency. RESULTS: The regression equation for the 25(OH)D concentration measured by the two method was y_(LC-MS/MS)=-0. 035+1. 007×x_(ELISA)(r=0. 877), and the average deviation between the two was 4. 48% and the intraclass correlation coefficient was 0. 87. The 25(OH)D concentration was less than 12 and 20 ng/mL as a criterion for vitamin D deficiency, and the Kappa coefficients were greater than 0. 60(0. 64 and 0. 74). CONCLUSION: When serum 25(OH)D level was detected by LC-MS/MS and ELISA, the correspondence of the two method was fine. Taking the "gold standard" LC-MS/MS method as a reference, the ELISA method was used to determine human vitamin D deficiency with good sensitivity and specificity, which can be used for the accurate and rapid detection of large-scale population samples.
Asunto(s)
Espectrometría de Masas en Tándem , Vitamina D , 25-Hidroxivitamina D 2 , Adolescente , Adulto , Cromatografía Liquida , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Persona de Mediana Edad , Vitamina D/análogos & derivados , Adulto JovenRESUMEN
KEY MESSAGE: ABA/GA4 ratio, stress resistance, carbon and nitrogen metabolism, and chromatin structure play important roles in vigour differences of seeds located at different maize ear positions. Seed vigour, which ensures rapid and uniform field emergence across diverse environments, differs at different maize ear positions. However, little is known regarding the associated mechanisms. In this study, we determined that seed vigour, stress resistance, and carbon and nitrogen metabolism were higher in seeds from middle and bottom section of the ear, while the ABA/GA4 ratio in the embryos was significantly lower. Compared with the seeds subjected to repeated pollination during silking, less variation in seed vigour and the ABA/GA4 ratio in the embryos was observed in seeds at different ear positions subjected to single pollination after complete silking. This indicated that single pollination can reduce, but not eliminate, the differences in seed vigour at different ear positions. RNA-seq analysis indicated that the seed vigour differences at the different locations of the maize ears of the single pollinated treatment were related to carbon and nitrogen metabolism. In contrast, the differences in seed vigour under repeated pollination were related to chromatin structure. The present study contributes to our understanding of the mechanisms underlying differences in seed vigour at different positions on the maize ear.
Asunto(s)
Adaptación Fisiológica , Reguladores del Crecimiento de las Plantas/metabolismo , Semillas/metabolismo , Análisis de Secuencia de ARN , Estrés Fisiológico , Zea mays/metabolismo , Ácido Abscísico/genética , Ácido Abscísico/metabolismo , Carbono/metabolismo , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Giberelinas/genética , Giberelinas/metabolismo , Nitrógeno/metabolismo , Reguladores del Crecimiento de las Plantas/genética , Polinización , ARN de Planta/análisis , Semillas/genética , Zea mays/genéticaRESUMEN
The aim of this study was to investigate the efficacy of anti-VEGF antibody-modified Paeonol liposome gels (PAE-BEV-lip gels) in the prevention and treatment of hypertrophic scars (HS). Systematic optimization of the encapsulation process of anti-VEGF antibody-modified Paeonol liposomes (PAE-BEV-lips) was performed using Box-Behnken design with the optimized parameters as follows: SPC concentration of 7.36 mg mL-1; SPC-Chol-PAE:pNP-PEG3000-DOPE:BVE-PEG3000-DOPE ratio of 14:5:4:0.28:0.05, w/w; the hydration temperature of 41 °C; stripping using pH 7.5 sodium dihydrogen phosphate buffer; and ultrasound for 3 min (ultrasound time 2 s, interval 3 s, power 300 W). Using these conditions, the encapsulation efficiency of PAE reached the peak level, i.e. 73.61 ± 2.36%. The PAE-BEV-lips displayed unimodal size-distribution with a mean diameter of (235.7 ± 4.67) nm and a zeta potential of -(5.13 ± 0.25) mV. The investigation of the retention effect PAE-BEV-lip gels revealed a slower transdermal delivery rate, a remarkable dermal retention effect, and superior bioavailability compared to PAE gels and PAE conventional liposome gels (PAE-lip gels). Meanwhile, PAE-BEV-lip gels exhibited definite effects on the prevention and treatment of HS of the rabbit ears. The PAE-BEV-lip gels group showed a lower scar proliferation rate, fewer and looser collagenous fibers and fibromyocytes, more regular chondrocytes, less calcified tissue and fewer inflammatory cells compared to other groups. At the same time, PAE-BEV-lip gels significantly reduced scar hyperplasia index (1.34 ± 0.51) and levels of VEGF, TGF-ß1 and TNF-α (30.90 ± 3.57, 733.2 ± 43.19 and 66.76 ± 2.98 ng·L-1, respectively), compared to the model group (p < .01).
Asunto(s)
Acetofenonas/farmacología , Anticuerpos/farmacología , Cicatriz Hipertrófica/tratamiento farmacológico , Liposomas/farmacología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Acetofenonas/química , Administración Cutánea , Animales , Anticuerpos/química , Disponibilidad Biológica , Química Farmacéutica/métodos , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Femenino , Geles/química , Geles/farmacología , Liposomas/química , Masculino , Ratones , Conejos , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To investigate the distribution and changes of blood copper, zinc, calcium, magnesium and iron in Chinese rural children aged 6 to 12 years in 2002 and 2012. METHODS: A total of 3420 blood samples were randomly selected from the China Nutrition and Health Survey 2002 and 2012. Metal concentrations in whole blood were determined by inductively coupled mass spectrometry(ICP-MS) after the dilution of 0. 5%(V/V) HNO_3 and 0. 05%(V/V) Triton-X-100. The changes between 2002 and 2012 of blood five elements concentration in children of 6-12 years in rural China were compared. RESULTS: The median of blood levels of copper, zinc, calcium, magnesium and iron in 2002 were 1. 02(95% CI 0. 79-1. 32), 4. 88(95% CI 3. 17-6. 77), 58. 59(95% CI 44. 97-74. 24), 41. 56(95% CI 33. 01-52. 28) and 423. 21(95% CI 338. 83-540. 69) mg/L, respectively. And in 2012, the median values were 1. 00(95% CI 0. 75-1. 31), 5. 12(95% CI 3. 17-7. 37), 63. 36(95% CI 41. 14-79. 16), 41. 78(95% CI 30. 89-52. 53) and 422. 06(95% CI 297. 83-522. 56) mg/L, respectively. There were significant differences in blood copper, zinc, calcium and iron levels in general, gender and age. There were also significant area differences in the distribution of copper, zinc, calcium, magnesium and iron, but the changes were opposite. CONCLUSION: In 2002 and 2012, there were differences in the blood distribution of Cu, Zn, Ca, Mg and Fe of children aged 6-12 in rural China in terms of general, gender, age and area.
Asunto(s)
Calcio/sangre , Cobre/sangre , Hierro/sangre , Magnesio/sangre , Zinc/sangre , Niño , China , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Espectrofotometría Atómica , OligoelementosRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with various clinical manifestations. MicroRNAs (miRNAs) and immunometabolism are recognized as key elements in SLE pathogenesis; however, the relationship between miRNAs in peripheral blood mononuclear cells (PBMCs) and metabolism in SLE remains unclear. METHODS: We detected PBMC miRNA and mRNA profiles from 3 pooled SLE patients and 3 healthy controls (HCs) using next-generation sequencing, predicted miRNA targets in dysregulated mRNAs, predicted functions and interactions of differentially expressed genes using bioinformatics analysis, validated candidate miRNAs using qRT-PCR, and investigated the association between the expression of candidate miRNAs and SLE clinical characteristics. Moreover, we validated the direct and transcriptional regulatory effect of NovelmiRNA-25 on adenosine monophosphate deaminase 2 (AMPD2) using a dual-luciferase reporter assay and western blot and confirmed AMPD2 mRNA and protein expression in PBMCs using qRT-PCR and western blot, respectively. RESULTS: Multilayer integrative analysis of microRNA and mRNA regulation showed that 10 miRNAs were down-regulated and 19 miRNAs were up-regulated in SLE patient PBMCs compared with HCs. Bioinformatics analysis of regulatory networks between miRNAs and mRNAs showed that 19 miRNAs were related to metabolic processes. Two candidate miRNAs, NovelmiRNA-25 and miR-1273h-5p, which were significantly increased in the PBMCs of SLE patients (P < 0.05), represented diagnostic biomarkers with sensitivities of 94.74% and 89.47%, respectively (area under the curve = 0.574 and 0.788, respectively). NovelmiRNA-25 expression in PBMCs was associated with disease activity in SLE patients, in both active and stable groups (P < 0.05). NovelmiRNA-25 overexpression downregulated AMPD2 expression in HEK293T cells through direct targeting of the AMPD2 3'UTR (P < 0.01), while inhibition of NovelmiRNA-25 activity led to increased AMPD2 expression (P < 0.01). NovelmiRNA-25 overexpression also downregulated AMPD2 protein expression in HEK293T cells; AMPD2 protein expression in SLE patient PBMCs was decreased. Our results show that differentially expressed miRNAs play an important role in SLE. CONCLUSIONS: Our data demonstrate a novel mechanism in SLE development that involves the targeting of AMPD2 expression by NovelmiRNA-25. miRNAs may serve as novel biomarkers for the diagnosis and evaluation of disease activity of SLE and represent potential therapeutic targets for this disease.
Asunto(s)
AMP Desaminasa/sangre , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/genética , MicroARNs/metabolismo , Secuencia de Bases , Biomarcadores/sangre , Estudios de Casos y Controles , Ontología de Genes , Redes Reguladoras de Genes , Células HEK293 , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: To establish the reference ranges of serum thyroid hormones and urine iodine in early pregnancy. METHODS: The study included 368 early pregnant women who underwent their routine antenatal care in Obstetric Clinic of Peking Union Medical College Hospital. The level of serum thyroid hormones was tested by automatic chemiluminescence immunoassay analyzer. The value of urine iodine was tested by inductively coupled plasma mass spectrometry. The reference ranges were decided by twoside limits( the 2. 5th and 97. 5th percentile values). RESULTS: The reference ranges of serum thyroid hormones in early pregnancy: FT3 3. 74- 5. 88 pmol/L, FT4 12. 54-20. 15 pmol/L, TSH 0. 12- 3. 48 mU/L. The reference ranges of individual urinary iodine concentration was 31- 543 µg/L. CONCLUSION: The reference ranges of serum thyroid hormones and individual urinary iodine in early pregnancy are established based on laboratory testing results.
Asunto(s)
Yodo/orina , Pruebas de Función de la Tiroides , Hormonas Tiroideas/sangre , Femenino , Humanos , Embarazo , Valores de ReferenciaRESUMEN
BACKGROUND: Peritoneal fibrosis is a common complication in patients treated with long-term peritoneal dialysis. The aim of this study was to identify the microRNAs (miRNAs) involved in regulation of peritoneal fibrosis in a rat model of peritoneal dialysis. METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly allocated into three groups: (i) Control group (Cg, n = 8); (ii) Saline group (Sg, n = 8): daily intraperitoneal injection with 0.9% normal saline; (iii) Hypertonic dialysate group (HDg, n = 8): daily intraperitoneal injection with 4.25% peritoneal dialysis solution. Rats were sacrificed after four weeks for histological evaluation of peritoneal membrane and the expression of α-SMA and COL-1. A miRNA screen was performed using microarray analysis to identify differentially expressed miRNAs, which were then validated by real-time PCR. RESULTS: Compared with the control and the saline groups, hypertonic dialysate group showed impaired peritoneal function accompanied by a spectrum of morphological changes including thicker peritoneal membrane, higher collagen deposition, infiltration of mononuclear cells and neovascularization in the peritoneum. Increased mRNA and protein levels of α-SMA and COL-1 were observed in hypertonic dialysate group, indicating the progression of peritoneal fibrosis. The miRNA screen identified 8 significantly down-regulated miRNAs (miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b) and one highly up-regulated miRNA (miR-122) in the hypertonic dialysate group. The results were confirmed by real-time PCR. CONCLUSIONS: Altered miRNA expression in peritoneum was found in the rat model of peritoneal fibrosis, indicating that these miRNAs may be associated with pathogenesis of peritoneal fibrosis.
Asunto(s)
MicroARNs/análisis , MicroARNs/fisiología , Diálisis Peritoneal , Fibrosis Peritoneal/genética , Animales , Modelos Animales de Enfermedad , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Background: Magnesium (Mg) is an essential element and participates in many metabolic pathways. Many studies have found a certain negative correlation between magnesium and blood glucose parameters, but the dose-response relationship between them is still a relatively narrow research field. We aim to explore the dose-response relationship between plasma and dietary Mg and type 2 diabetes (T2DM) among childbearing women in a nationally representative sample. And we will also initially explore the threshold of dietary and plasma magnesium in the prevention of T2DM and their consistency. Methods: A total of 2912 18-44 year-old childbearing women were recruited from the China Adult Chronic Disease and Nutrition Surveillance (2015). Multivariate logistic regression was used to explore the dose-response relationship between plasma and dietary Mg and glucose parameters. The threshold effect between Mg and T2DM was explored by a restricted cubic spline regression. Results: It was found that when plasma Mg was increased by 0.041 mmol/L, the risk of T2DM, impaired fasting glucose (IFG), and HbA1c-hyperglycemia was reduced by 18%, 19%, and 18%, respectively. The possible threshold value for plasma Mg to prevent the risk of T2DM was 0.87 mmol/L. Through the quality control of the sample dietary survey data, 2469 cases were finally included for dietary analysis. And the possible threshold value for dietary Mg to prevent the risk of T2DM was 408 mg/d. Taking the recommended dietary Mg intake of 330 mg/d as the reference group, when the Mg intake reached 408 mg/d, the risk of T2DM was significantly reduced. And the average plasma Mg level of the people whose dietary intake reached 408 mg/d was 0.87 mmol/L. Conclusions: These results indicate that dietary Mg and plasma Mg have good consistency on the threshold effect of glucose parameters in women of childbearing age.
Asunto(s)
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Femenino , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Magnesio , China/epidemiología , Enfermedad Crónica , GlucosaRESUMEN
Oxygenated organic molecules (OOMs) are recognized as important precursors for new particle formation (NPF) in the urban atmosphere. The paper theoretically studied the formation of OOMs by styrene oxidation processes initiated by OH radicals, focusing on the OOMs nucleation mechanism. The results found that in the presence of an H2SO4 molecule, lowly oxygenated organic molecules containing a benzene ring (LOMBs) can form stable clusters and grow to the scale of a critical nucleus through pi-pi stacking and OH hydrogen bonding. In addition, LOMBs are more readily generated in a styrene-oxidized system in the presence/absence of NOx than highly oxygenated organic molecules (HOMs). The reaction of OH radicals with other aromatics containing a branched chain on the benzene ring produces LOMBs to varying degrees, with pi-pi stacking playing an essential role. This result suggests that, in the presence of H2SO4 molecules, LOMBs may play a more significant role in promoting nucleation than HOMs. Our findings serve as a pivotal foundation for future investigations into the oxidation and nucleation processes of diverse aromatics in urban environments.
RESUMEN
Purpose: Magnesium (Mg) is an essential nutrient for the maintenance of vital physiological functions. Magnesium deficiency is associated with diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS); however, conclusions have been inconsistent, and there is a particular lack of evidence regarding this association in Chinese population older than 45 years. This study aimed to assess the association between plasma magnesium and the risk of MetS and its components, the dose-response relationship, and the threshold effect relationship in a Chinese population involving older than 45 years. Methods: A total of 2,101 individuals were randomly selected from the China Nutrition and Health Surveillance (CNHS) (2015-2017) by considering monitoring points. We used the joint statement of the International Diabetes Federation (IDF) in 2009 to define participants with MetS. The plasma magnesium was tested by inductively coupled plasma mass spectrometry (ICP-MS). The logistic regression and restricted cubic spline (RCS) models were used to analyze the association and dose-response relationship between plasma Mg and MetS and its components. Results: Compared with the lowest quintile (Q1) for plasma Mg, the odds ratios (ORs) and 95% confidence intervals (95% CI) for MetS, impaired fasting glucose (IFG), hypertension, and triglyceride (TG) elevation at the highest quintile (Q5) were 0.419 (0.301, 0.583), 0.303 (0.221, 0.415), 0.446 (0.322, 0.618), and 0.526 (0.384, 0.720), respectively, with all p < 0.05. However, in the components of decreased high-density lipoprotein cholesterol (HDL-C) and central obesity, no trend toward lowering with higher plasma magnesium was observed (p = 0.717, p = 0.865). These associations were not altered by further adjustment for potential confounding variables, including age, gender, education, nationality, area, residence, body mass index (BMI), and heart rate. The RCS analysis showed that, when plasma magnesium was lower than 0.85 mmol/L, the curve was leveled off, and then, the curve showed a decreasing trend with the increase in plasma magnesium. Conclusion: Therefore, plasma Mg was negatively associated with MetS and its components (including IFG, hypertension, and elevated TG) in people older than 45 years. In addition, plasma Mg greater than or equal to 0.85 mmol/L, which is higher than the commonly used threshold of 0.75 mmol/L, may be protective against MetS and its components (including elevated FPG, elevated blood pressure, and elevated TG). More prospective studies, such as randomized controlled trials, are necessary to confirm the effective impact of Mg on MetS and its components. Plasma Mg levels in the MetS population older than 45 years require attention.
RESUMEN
Purpose: Acute Myocardial Infarction (AMI) is globally prevalent, with oxidative stress as a key contributor to its pathogenesis. This study aimed to explore oxidative stress-related genes as potential AMI biomarkers, elucidating their role in disease progression. Patients and Methods: Gene expression data from AMI samples in the Gene Expression Omnibus (GEO) database and oxidative stress-related genes (OSRGs) from the GeneCards database were extracted. Weighted Gene Co-expression Network Analysis (WGCNA) identified key module genes associated with AMI. Intersecting OSRGs, key module genes, and differentially expressed genes (DEGs) between AMI and normal samples led to the extraction of differentially expressed ORSGs (DE-ORSGs) related to AMI. Feature genes were mined using the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) algorithm, followed by potential diagnostic value assessment using receiver operating characteristic (ROC) curves. Gene Set Enrichment Analysis (GSEA) was executed on the identified key genes. Immune infiltration levels were explored using the CIBERSORT algorithm, and a Transcription Factor (TF) -mRNA regulatory network of key genes was created. The key genes were validated using qRT-PCR. Results: We authenticated three key genes (MMP9, TGFBR3, and S100A12) from 6 DE-ORSGs identified in AMI. GSEA revealed that these key genes were enriched in immune-related signaling pathways. Immune infiltration analysis identified three differential immune cell types (resting NK cells, Monocytes, and M0 Macrophages) between AMI and normal groups. Correlation analysis revealed positive associations of MMP9 with M0 Macrophages and S100A12 with Monocytes and M0 Macrophages, whereas TGFBR3 was negatively related to Monocytes. A TF-mRNA regulatory network was generated based on these key genes. qRT-PCR validation confirmed the differential expression of S100A12 and TGFBR3 between AMI and control samples. Conclusion: TGFBR3, and S100A12 were identified as potential oxidative stress-related biomarkers in AMI, providing new insights for AMI diagnosis and treatment.
RESUMEN
China is gradually transitioning from the "tunnel construction exploration era" to the "tunnel high-quality construction and operation era", and the maintenance demand of highway tunnels has increased sharply. Therefore, there is an urgent need for an evaluation method to evaluate the service reliability of highway tunnels, so as to provide reference for tunnel maintenance personnel to carry out maintenance work. Taking highway tunnels as the research object, this paper extracts three parameters, including length, maximum width and fractal dimension, from the binary image of highway tunnel lining cracks. The standard for dividing the length of the highway tunnel section is 500m as the tunnel section, and a section disease sample space including multiple highway tunnels is constructed. The EM clustering algorithm was used to determine the number of graded grades of disease, and the relative Euclidean distance was used as the evaluation index to divide the safety grade of the tunnel into five grades: normal, degraded, inferior, deteriorated and hazardous. The partial least squares method is used to establish the lining service reliability evaluation formula and verify the residual of each sample point in the sample space. The smaller the average value of the residual, the better fitting effect of the established evaluation formula. The service reliability evaluation method proposed in this paper is applied to engineering practice and compared with the expert scoring method and the national standard method, which proves that the evaluation method in this paper has the advantages of strong visibility, simple evaluation method, and is conducive to engineering practice.